Change in blood eosinophils following treatment with inhaled corticosteroids may predict long-term clinical response in COPD
- Alexander G. Mathioudakis1,2,
- Andras Bikov1,2,
- Philip Foden3,
- Lies Lahousse4,
- Guy Brusselle5,6,
- Dave Singh1,2,7 and
- Jørgen Vestbo1,2
- 1Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, UK
- 2North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
- 3Department of Medical Statistics, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
- 4Department of Bioanalysis, Ghent University, Ghent, Belgium
- 5Departments of Epidemiology and Respiratory Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
- 6Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
- 7Medicines Evaluation Unit, Manchester, UK
- Prof. Jørgen Vestbo DMSc, FRCP, FERS, FMedSci, Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, UK. E-mail: jorgen.vestbo{at}manchester.ac.uk
Abstract
There is an emerging role for blood eosinophil count (EOS) as a biomarker to guide inhaled corticosteroid (ICS) therapy in COPD. Since ICS administration could influence EOS, we hypothesised that change in EOS following treatment with ICS may predict outcomes of long-term therapy.
In a post-hoc analysis of ISOLDE, a three-year, double-blind trial comparing 500 µg fluticasone propionate BID with placebo in 751 patients with moderate-to-severe COPD, we evaluated whether the initial changes in EOS during ICS treatment were predictive of ICS treatment response.
EOS change within 1 year after the introduction of ICS was strongly predictive of treatment response. A suppressed EOS was associated with treatment effect. Characteristically, in patients with EOS suppression of ≥200 EOS·μL−1, ICS use was associated with a decelerated FEV1 decline rate, by 32 mLs·year−1, and 30% reduction in the exacerbation rate. In contrast, in patients experiencing an increase in EOS of ≥200 EOS·μL−1, ICS use was associated with an accelerated FEV1 decline rate by 37 mLs·year−1 and an increased exacerbation rate by 80% (p<0.0001). EOS change was not predictive of clinical response with regards to health status evaluated using Saint George Respiratory Questionnaire.
These findings suggest EOS change after ICS administration may predict clinical response to ICS therapy in patients with moderate-to-severe COPD at risk of exacerbations. ICS administration may be associated with more frequent exacerbations and an accelerated lung function decline in the 20% of patients where EOS increases after the administration of ICS. These hypothesis-generating observations will need validation in prospectively designed studies.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Mathioudakis reports grants from Boehringer Ingelheim, personal fees from Boehringer Ingelheim, personal fees from GlaxoSmithKline, outside the submitted work.
Conflict of interest: Dr. Bikov has nothing to disclose.
Conflict of interest: Philip Foden has nothing to disclose.
Conflict of interest: Dr. Lahousse reports grants from AstraZeneca, grants from Chiesi, personal fees from Boehringer Ingelheim, personal fees from Novartis, outside the submitted work.
Conflict of interest: Dr. Brusselle reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Teva, personal fees from Sanofi, outside the submitted work.
Conflict of interest: Dr. Singh reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Chiesi, personal fees from Cipla, personal fees from Genentech, grants and personal fees from GlaxoSmithKline, grants and personal fees from Glenmark, grants and personal fees from Menarini, grants and personal fees from Mundipharma, grants and personal fees from Novartis, personal fees from Peptinnovate, grants and personal fees from Pfizer, grants and personal fees from Pulmatrix, grants and personal fees from Therevance, grants and personal fees from Verona, outside the submitted work.
Conflict of interest: Dr. Vestbo reports personal fees from Chiesi Pharmaceuticals, personal fees from Boehringer-Ingelheim, personal fees from Novartis, personal fees from AstraZeneca, outside the submitted work.
This is a PDF-only article. Please click on the PDF link above to read it.
- Received June 30, 2019.
- Accepted February 17, 2020.
- Copyright ©ERS 2020